Cyclodextrins are cyclic alpha-1,4-oligosaccharide starch derivates. Alpha, beta, gamma, and delta cyclodextrins are known, containing six, seven, eight, and nine glucose units respectively. Their importance lies in their enzymic properties attributed to their hollow truncated cone structure having primary 6-hydroxyls at the narrower end, and secondary 2- and 3-hydroxyls at the wider end, a relatively hydrophobic interior cavity and a relatively hydrophilic exterior.
The cyclodextrins form inclusion complexes and it is believed that these inclusion complexes and similar compounds modify the chemical and physical environment affecting chemical reactions to induce chirality in otherwise achiral reactions. The cyclodextrins are themselves inherently chiral being composed of chiral D-glucose units.
Substituted aminodeoxy cyclodextrins are particularly noted for their chiral catalytic effects (Tagaki et al., Tetrahedron Lett., 1990, 31, 3897-3900, Parrot-Lopez et al., Tetrahedron: Asymmetry, 1990, 1, 367-370, Angew. Chem. Int. Ed. Engl., 1992, 31, 1381-1383, incorporated herein by reference).
Azidodeoxy cyclodextrins are suitable precursors for aminodeoxy cyclodextrins.
It is a principal object of the invention to prepare azidodeoxy cyclodextrins and their amino derivatives.
In accordance with a broadest aspect of an embodiment of the invention there is provided a compound of formula ##STR1## wherein C is cyclodextrin, A is amino, azido or aminocarbonyl aralkoxy, wherein said aralkoxy has 7 to 10 carbon atoms and n is 0, 1, 2 or 3, B is hydroxyl, or one of A and B is azido and the other is aminocarbonyl aralkoxy, R is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, aminoalkyl of 1 to 6 carbon atoms, azidoalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alkylcarboalkoxy in which the alkyl and alkoxy groups have 1 to 6 carbon atoms each, with the proviso when R is aminoalkyl, azidoalkyl, or haloalkyl n is 0.
In a broadest aspect of another embodiment of the invention there is provided a process of preparation of a compound of formula ##STR2## wherein C is cyclodextrin, A is amino, azido or aminocarbonyl aralkoxy, wherein said aralkoxy has 7 to 10 carbon atoms and n is 0, 1, 2 or 3, B is hydroxyl, or one of A and B is azido and the other is aminocarbonyl aralkoxy, R is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, amin alkyl of 1 to 6 carbon atoms, azidoalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alkylcarboalkoxy in which the alkyl and alkoxy groups have 1 to 6 carbon atoms each, with the proviso when R is aminoalkyl, azidoalkyl, or haloalkyl n is 0. When A is azido, B is hydroxyl, n is 1, 2, or 3, a cyclodextrin of formula I, wherein C is cyclodextrin, B is hydroxyl, R is hydrogen, alkyl of 1 to 6 carbon atoms, or alkenyl of 2 to 6 carbon atoms, is reacted with alkali metal azide triphenyl phosphine, and carbon tetrabromide. When A is azido, B is aminocarbonyl aralkoxy, wherein said aralkoxy has 7 to 10 carbon atoms, n is 1, 2, or 3, a cyclodextrin of formula I, wherein C is cyclodextrin, A is aminocarbonyl aralkoxy, wherein said aralkoxy has 7 to 10 carbon atoms, B is hydroxyl, R is hydrogen, alkyl of 1 to 6 carbon atoms, or alkenyl of 2 to 6 carbon atoms, is reacted with alkali metal azide triphenyl phosphine, and carbon tetrabromide. When A is amino, B is hydroxyl, n is 1, 2, or 3, a cyclodextrin of formula I, wherein C is cyclodextrin, A is azido, B is hydroxyl, R is hydrogen, alkyl of 1 to 6 carbon atoms, or alkenyl of 2 to 6 carbon atoms, is reacted with hydrogen in the presence of palladium on charcoal. When A is aminocarbonyl aralkoxy, B is hydroxyl, n is 1, 2, or 3, a cyclodextrin of formula I wherein C is cyclodextrin, A is azido, B is hydroxyl, R is hydrogen, alkyl of 1 to 6 carbon atoms, or alkenyl of 2 to 6 carbon atoms, is reacted with sodium bicarbonate and aralkyl chloroformate, wherein said aralkyl has 7 to 10 carbon atoms. When n is 0, B is hydroxyl, R is azidoalkyl of 1 to 6 carbon atoms cyclodextrin is reacted with alkali metal hydride in a first step, and the product thereof with haloazidoalkane in a second step. When n is 0, B is hydroxyl, R is aminoalkyl of 1 to 6 carbon atoms, a cyclodextrin of formula I, wherein n is 0, B is hydroxyl, R is azidoalkyl of 1 to 6 carbon atoms is reacted with triphenylphosphine in the presence of ammonia. When n is 0, B is hydroxyl, R is alkyl of 1 to 6 carbon atoms or alkenyl of 2 to 6 carbon atoms cyclodextrin is reacted with alkali metal hydride in a first step and the product thereof with a reagent selected from the group consisting of alkyl or alkenyl iodides, and their bromo and chloro analogs in the presence of alkali metal iodide in a second step. When n is 0, B is hydroxyl, R is haloalkyl of 1 to 6 carbon atoms cyclodextrin is reacted with alkali metal hydride in a first step and the product thereof with a reagent selected from the group consisting of alpha-omega iodohaloalkanes, and their bromohalo analogs in the presence of alkali metal iodide in a second step.
In accordance with one aspect of one embodiment of the present invention there is provided a compound of formula ##STR3## wherein C is cyclodextrin, A is azido and n is 0, 1, 2 or 3, R is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, or azidoalkyl of 1 to 6 carbon atoms, with the proviso when R is azidoalkyl, n is 0.
In another aspect of the present invention, there is provided a process of preparation of a compound of formula ##STR4## wherein C is cyclodextrin, A is azido and n is 0, 1, 2 or 3, R is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, or azidoalkyl of 1 to 6 carbon atoms, with the proviso when R is azidoalkyl, n is 0, comprising when n is 1, 2, or 3 reacting a cyclodextrin of formula ##STR5## wherein C is cyclodextrin, R is hydrogen, alkyl of 1 to 6 carbon atoms, or alkenyl of 2 to 6 carbon atoms, with alkali metal azide triphenylphosphine, and carbon tetrabromide, when n is 0 reacting cyclodextrin with alkali metal hydride in a first step, and the product thereof with haloazidoalkane in a second step.